Document Detail

Inferring relevant control mechanisms for interleukin-12 signaling in naïve CD4+ T cells.
MedLine Citation:
PMID:  20479776     Owner:  NLM     Status:  MEDLINE    
Interleukin-12 (IL-12) is a key cytokine involved in shaping the cell-mediated immunity to intracellular pathogens. IL-12 initiates a cellular response through the IL-12 signaling pathway, a member of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) family of signaling networks. The JAK/STAT pathway includes several regulatory elements; however, the dynamics of these mechanisms are not fully understood. Therefore, the objective of this study was to infer the relative importance of regulatory mechanisms that modulate the activation of STAT4 in naïve CD4(+) T cells. Dynamic changes in protein expression and activity were measured using flow cytometry and these data were used to calibrate a mathematical model of IL-12 signaling. An empirical Bayesian approach was used to infer the relative strengths of the different regulatory mechanisms in the system. The model predicted that IL-12 receptor expression is regulated by a dynamic, autonomous program that was independent of STAT4 activation. In summary, a mathematical model of the canonical IL-12 signaling pathway used in conjunction with a Bayesian framework provided high-confidence predictions of the system-specific control mechanisms from the available experimental observations.
Stacey D Finley; Deepti Gupta; Ning Cheng; David J Klinke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-18
Journal Detail:
Title:  Immunology and cell biology     Volume:  89     ISSN:  1440-1711     ISO Abbreviation:  Immunol. Cell Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-06     Completed Date:  2011-12-16     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8706300     Medline TA:  Immunol Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  100-10     Citation Subset:  IM    
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MeSH Terms
CD4-Positive T-Lymphocytes / immunology*,  metabolism
Cell Culture Techniques
Interleukin-12 / immunology*,  metabolism*
Mice, Inbred BALB C
Models, Immunological
Receptors, Interleukin-12 / metabolism
STAT4 Transcription Factor / metabolism
Signal Transduction*
Spleen / cytology,  immunology
Grant Support
R15 CA132124/CA/NCI NIH HHS; R15 CA132124-01A2/CA/NCI NIH HHS; R15 CA132124-01A2S2/CA/NCI NIH HHS; R15 CA132124-01A2S3/CA/NCI NIH HHS; R15CA123123/CA/NCI NIH HHS; R21 AI076221/AI/NIAID NIH HHS; R21 AI076221-01A1/AI/NIAID NIH HHS; R56 AI076221/AI/NIAID NIH HHS; R56 AI076221-01A1/AI/NIAID NIH HHS; R56AI076221/AI/NIAID NIH HHS
Reg. No./Substance:
0/Receptors, Interleukin-12; 0/STAT4 Transcription Factor; 187348-17-0/Interleukin-12

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